Immuntherapie oder zielgerichtete Therapie mit oder ohne Radiotherapie für Patienten mit Melanom oder nicht-kleinzelligem Lungenkarzinom, das sich ins Gehirn ausgebreitet hat

Radiation: Stereotactic radiosurgery;Drug: Immune checkpoint inhibitor

Gender: All
Maximum age: N/A
Minimum age: 18 Years

Inclusion Criteria:

1. Newly diagnosed, previously untreated (except for surgery, see below) asymptomatic or
oligo-symptomatic brain metastases, e.g., controlled symptomatic seizure disorder.
Note: patients with neurological symptoms or signs that require more than a stable
dose of 4 mg dexamethasone equivalent for more than one week, are not considered
oligo-symptomatic.

Requirements for brain metastases:

- Brain metastases must be previously untreated, except for surgery.

- Prior surgery (including biopsies, resection, and cyst aspiration) for brain
metastases is allowed. Residual and measurable disease after surgery is not
required, but surgery must have confirmed the diagnosis. An MRI performed within
72 hours post-surgery should be available.

- Number and size of metastases at diagnosis of brain metastases (as per Yamamoto
et al.7):

- Maximum 1-10 brain metastases

- At least one brain metastasis must be of =5 mm in diameter

- In case of 1-4 brain metastases:

- Longest diameter of largest brain metastasis must be =30 mm

- In case of 5-10 brain metastases:

- Largest metastasis must be =10 mL in volume and longest diameter must be =30 mm

- Maximum cumulative brain metastases volume must be =30 mL

2. Primary disease of histologically confirmed (from primary tumour or from a metastatic
lesion, including in the brain) melanoma or NSCLC

Requirements for patients with melanoma:

- Prior treatment, including treatment with immune-checkpoint inhibitors is
permitted, but brain metastases must be newly diagnosed and previously untreated
(except for surgery).

- BRAF-mutation status, locally assessed, should be known (previous BRAF-targeted
therapy is allowed).

Requirements for patients with NSCLC:

- Newly diagnosed, treatment-na?ve (except for prior surgery) metastatic NSCLC,
with or without a targetable oncogenic driver alteration: sensitising
EGFR-mutation (exon 19-del and 21-L858R), ALK- or ROS1-fusion.

- Known PD-L1 expression status (from primary tumour or from a metastatic lesion,
including brain)

- Known driver mutation status (from primary tumour or from a metastatic lesion,
including brain).

3. Age of 18 years or older

4. Karnofsky performance status of 60 or more

5. Life expectancy >12 weeks

6. Patients must be candidates for systemic treatment, with one of the following
treatment cohorts planned:

- Immune-checkpoint inhibition therapy (combination of ipilimumab and nivolumab)
for metastatic melanoma with or without a BRAF-mutation.

- anti-PD-1/L1 monotherapy for metastatic melanoma with or without a BRAF-mutation.

- targeted therapy for metastatic NSCLC with targetable oncogenic driver alteration
(EGFR-mutation or ALK- or ROS1-fusion).

- Immune-checkpoint inhibition therapy (including an anti-PD-1/L1 compound) alone
or in combination with chemotherapy for metastatic NSCLC without targetable
oncogenic driver alteration.

7. Women of childbearing potential, including women who had their last menstruation in
the last 2 years, must have a negative urinary or serum pregnancy test within 7 days
before randomisation.

8. Written IC for study participation must be signed and dated by the patient and the
investigator prior to any study-related intervention.

Exclusion Criteria:

1. Confirmed or probable leptomeningeal metastasis according to EANO ESMO criteria1

2. Symptomatic brain metastases at time of randomisation, e.g., neurological symptoms or
signs that require more than a stable dose of 4 mg dexamethasone equivalent for more
than one week.

- Patients must be off steroids or on a stable dose of =4 mg dexamethasone
equivalent for one week prior to randomisation.

- Patients experiencing seizures controlled by anti-epileptic drugs are eligible.

3. Prior whole brain irradiation or focal radiation therapy to the brain

4. Prior systemic treatment for brain metastases

5. Contra-indication for SRS

6. For patients with NSCLC: any previous anticancer systemic therapy other than those
under investigation in this study.

7. Judgment by the investigator that the patient should not participate in the study if
the patient is unlikely to comply with study procedures, restrictions and
requirements.

8. Women who are pregnant or in the period of lactation.

9. Sexually active men and women of childbearing potential who are not willing to use an
effective contraceptive method during the study.